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This paper provides a comprehensive summary of evidence to explore and position the role of serology testing in the context of coronavirus disease 19 (COVID-19) immunization and policy response in the Asia-Pacific (APAC) region. The document builds on a review of academic literature and existing policies followed by a process of discussion, validation, and feedback by a group of six experts. Six countries and territories—Australia, Hong Kong, India, Indonesia, Thailand, and Taiwan—were sampled to highlight the differing contexts and scenarios in the region. The review includes an overview of (1) the impact of the COVID-19 pandemic, including the emergence of Variants of Concern (VOCs), especially Omicron, (2) the introduction of immunization, (3) the available testing options and potential use of serology testing, (4) the landscape of guidelines and recommendations for their use, and (5) the barriers and challenges to implementing serology testing as a tool to support COVID-19 immunization. Based on the findings, the co-authors propose a set of recommendations to resolve knowledge gaps, to include the use of serology testing as part of the policy response, and to ensure adequate means of implementation. This paper’s target audience includes members of the academic community, medical societies, health providers and practitioners, and decision-makers.

Background: The coronavirus disease 2019 (COVID-19) pandemic has had a devastating impact worldwide, and timely detection and quarantine of infected patients are critical to prevent spread of disease. Serological antibody testing is an important diagnostic method used increasingly in clinics, although its clinical application is still under investigation. Methods: A meta-analysis was conducted to compare the diagnostic performance of severe acute respiratory syndrome coronavirus-2 antibody tests in patients with COVID-19. The test results analysed included: (1) IgM-positive but IgG-negative (IgM+IgG−); (2) IgG-positive but IgM-negative (IgG+IgM−); (3) both IgM-positive and IgG-positive (IgM+IgG+); (4) IgM-positive without IgG information (IgM+IgG+/−); (5) IgG-positive without IgM information (IgG+IgM+/−); (6) either IgM-positive or IgG-positive (IgM+ or IgG+); and (7) IgA-positive (IgA+). Results: Sixty-eight studies were included. Pooled sensitivities for IgM+IgG−, IgG+IgM−, IgM+IgG+, IgM+IgG+/−, IgG+IgM+/−, and IgM+ or IgG+ were 6%, 7%, 53%, 68%, 73% and 79% respectively. Pooled specificities ranged from 98% to 100%. IgA+ had a pooled sensitivity of 78% but a relatively low specificity of 88%. Tests conducted 2 weeks after symptom onset showed better diagnostic accuracy than tests conducted earlier. Chemiluminescence immunoassay and detection of S protein as the antigen could offer more accurate diagnostic results. Discussion: These findings support the supplemental role of serological antibody tests in the diagnosis of COVID-19. However, their capacity to diagnose COVID-19 early in the disease course could be limited.

Novel coronavirus (nCoV) first emerged in Hubei province of China in December 2019. The virus initially known as 2019-nCoV was renamed to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses. The associated disease is known as coronavirus disease 2019 (COVID-19). As the COVID-19 pandemic has unfolded, interest has grown in antibody testing as a way to measure how far the infection has spread and to identify individuals who may be immune. Molecular diagnostic tests like polymerase chain reaction are developed rapidly, however they are not able to fulfill all the requirements of an epidemic reaction. Hence, to complement molecular diagnostic tests, serology tests emerged as a vital aspect of the overall response by confirming the presence of antibodies during the early stage of the infection. Antibody tests help in assessing herd immunity, data about the ongoing phase of infection, identifying potential donors for convalescent plasma therapy, etc. This review currently focuses on giving an overview about the antibody tests in SARS-CoV-2 infections.

BackgroundMore than 200 countries are experiencing the coronavirus disease (COVID-19) pandemic. COVID-19 vaccination strategies have been implemented worldwide, and repeat COVID-19 outbreaks have been seen. The purpose of this study was to investigate the impact of COVID-19 vaccination on the reduction of perceived anxiety and the association between public anxiety and antibody testing intention during the COVID-19 pandemic.MethodsChinese adults aged 18 and over were surveyed using an anonymous online questionnaire in April and May 2021. The questionnaire collected sociodemographic characteristics, vaccination characteristics, perceived anxiety due to COVID-19, and attitudes toward future antibody testing after COVID-19 vaccination. Perceived anxiety was assessed on a visual analog scale (VAS). Multivariate logistic regression analysis was used to determine the factors influencing future antibody detection.ResultsA total of 3,233 people were investigated, 3,209 valid questionnaires were collected, and the response rate was 99.3%. Of the 3,209 respondents, 2,047 were vaccinated, and 1,162 were unvaccinated. There was a significant difference in anxiety levels between vaccinated and unvaccinated respondents (24.9±25.4 vs. 50.0±33.1, respectively). With the local spread of COVID-19 in mainland China, the public anxiety VAS scores increased by 15.4±25.6 (SMD=120%) and 33.8±31.7 (SMD=49%) among vaccinated and unvaccinated respondents, respectively. Of the 2,047 respondents who were vaccinated, 1,626 (79.4%) thought they would accept antibody testing. Those who displayed more anxiety about acquiring COVID-19 disease were more likely to accept COVID-19 antibody testing. If the antibody test results showed protective antibodies, 1,190 (58.1%) were more likely to arrange travel plans in China, while 526 (25.7%) thought they would feel safer traveling abroad.ConclusionCOVID-19 vaccination strategies help reduce public anxiety. However, public anxiety may be elevated as the local transmission of COVID-19 occurs in mainland China, which is usually caused now by imported cases. Those who display more anxiety choose to have antibody testing. Improving the accessibility of COVID-19 antibody tests can help ease public anxiety and enhance the confidence of some people to participate in social activities.

A novel clinical assay for the detection and quantitation of antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was adapted from an in-house, research-based enzyme-linked immunosorbent assay (ELISA). Development and validation were performed under regulatory guidelines, and the test obtained emergency use authorization (EUA) from the New York State Department of Health (NYSDOH) and the Food and Drug Administration (FDA). The Mount Sinai coronavirus disease 2019 (COVID-19) antibody assay is an orthogonal, quantitative direct ELISA test which detects antibodies reactive to the receptor binding domain (RBD) and the spike protein of the novel SARS-CoV-2. The assay is performed on 96-well plates coated with either SARS-CoV-2 recombinant RBD or spike proteins. The test is divided into two stages, a qualitative screening assay against RBD and a quantitative assay against the full-length spike protein. The test uses pooled high titer serum as a reference standard. Negative pre-COVID-19 and positive post-COVID-19, PCR-confirmed specimens were incorporated in each ELISA test run, and the assays were performed independently at two different locations.The Mount Sinai COVID-19 serology performed with high sensitivity and specificity, 92.5% (95% CI: 0.785–0.980) and 100% (CI: 0.939–1.000) respectively. Between-run precision was assessed with a single run repeated over 22 days; and within-run precision was assessed with 10 replicates per day over 22 days. Both were within reported acceptance criteria (CV ≤ 20%).This population-based study reveals the applicability and reliability of this novel orthogonal COVID-19 serology test for the detection and quantitation of antibodies against SARS-CoV-2, allowing a broad set of clinical applications, including the broad evaluation of SARS-CoV-2 seroprevalence and antibody profiling in different population subsets.

The emergence of the new coronavirus SARS-CoV-2 in late 2019 led to the global pandemic COVID-19, causing a profound socioeconomic crisis. Adequate diagnostic tools need to be developed to control the ongoing spread of infection. Virus-specific humoral immunity in COVID-19 patients and those vaccinated with specific vaccines has been characterized in numerous studies, mainly using Spike protein-based serology tests. However, Spike protein and specifically its receptor-binding domain (RBD) are mutation-prone, suggesting the reduced sensitivity of the validated serology tests in detecting antibodies raised to variants of concern (VOC). The viral nucleocapsid (N) protein is more conserved compared to Spike, but little is known about cross-reactivity of the N-specific antibodies between the ancestral B.1 virus and different VOCs. Here, we generated recombinant N phosphoproteins from different SARS-CoV-2 strains and analyzed the magnitude of N-specific antibodies in COVID-19 convalescent sera using an in-house N-based ELISA test system. We found a strong positive correlation in the magnitude of anti-N (B.1) antibodies and antibodies specific to various VOCs in COVID-19-recovered patients, suggesting that the N-binding antibodies are highly cross-reactive, and the most immunogenic epitopes within this protein are not under selective pressure. Overall, our study suggests that the RBD-based serology tests should be timely updated to reflect the constantly evolving nature of the SARS-CoV-2 Spike protein, whereas the validated N-based test systems can be used for the analysis of sera from COVID-19 patients regardless of the strain that caused the infection.

A new pandemic is ongoing in several parts of the world. The agent responsible is the newly emerged severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). The symptoms associated with this virus are known as the coronavirus disease-2019 (COVID-19). In this review, we summarize the published data on virus specific antibodies in hospitalized patients with COVID-19 disease, patients recovered from the disease and the individuals who are asymptomatic with SARS-CoV-2 infections. The review highlights the following: i) an adjunct role of antibody tests in the diagnosis of COVID-19 in combination with RT-PCR; ii) status of antibodies from COVID-19 convalescent patients to select donors for plasma therapy; iii) the potential confounding effects of other coronaviruses, measles, mumps and rubella in antibody testing due to homology of certain viral genes; and iv) the role of antibody testing for conducting surveillance in populations, incidence estimation, contact tracing and epidemiologic studies.

This review aims to explore the role and value of serology testing in the context of COVID-19 immunization policies in Latin American countries and the barriers and challenges to the adequate use and uptake of this tool. It builds on a review of the academic literature, evidence, and existing policies, and includes a multistage process of discussion and feedback by a group of five experts. Regional and country-level evidence and resources from five focus countries—Argentina, Brazil, Chile, Colombia, and Mexico—were collected and analyzed. This review contains an overview of (1) the impact of the SARS-CoV-2 pandemic, the variants of concern and current testing strategies, (2) the introduction of COVID-19 vaccination, (3) the potential use of serology testing to support immunization initiatives, (4) the current frameworks for the use of serology testing in the region, and (5) the barriers and challenges to implementing serology testing in the context of COVID-19 immunization policies, including a discussion on the potential actions required to address these barriers and facilitate the uptake of this strategy in the region. Stakeholders can use elements of this document to guide timely decision-making, raise awareness, and inspire further studies.

SARS-CoV-2 infection has generated the biggest pandemic since the influenza outbreak of 1918–1919. One clear difference between these pandemics has been the ability to test for the presence of the virus or for evidence of infection. This review examined the performance characteristics of sample types via PCR detection of the virus, of antibody testing, of rapid viral antigen detection kits and computerised tomography (CT) scanning. It was found that combined detection approaches, such as the incorporation of CT scans, may reduce the levels of false negatives obtained by PCR detection in both symptomatic and asymptomatic patients, while sputum and oral throat washing sample types should take precedence over swabbing when available. Rt-PCR assays for detection of the virus remain the gold-standard method for SARS-CoV-2 diagnosis and can be used effectively on pooled samples for widespread screening. The novel Oxford antibody assay was found to have the highest sensitivity and specificity of four currently available commercial antibody kits but should only be used during a specific timeframe post-symptom onset. Further research into transmission modes between symptomatic and asymptomatic patients is needed. Analysis of the performance characteristics of different sampling and detection methods for SARS-CoV-2 showed that timing of sampling and testing methods used can greatly influence the rate of false-positive and false-negative test results, thereby influencing viral spread.

In situations of diagnostic tests studies where the gold standard (GS) test is not absolutely perfect, validity measures of index tests vary in subgroups with varying disease prevalence. This is called reference standard misclassification. Although this is widely known, little is explained about the variations in the performance of index tests when the validity of the GS test itself varies with the time duration of illness. This article attempts to expand the concept of reference standard misclassification specifically on the effect of time dependence of diagnostic tests. A brief literature review is also presented which documents the existent knowledge among researchers about the concept and the methods they usually employ to adjust. A list of solutions which can address the issue has also been discussed to enable researchers to design and analyse diagnostic test studies in better ways.